DESCRIPTION: Diabetic retinopathy is a leading cause of blindness, while diabetic nephropathy is a leading cause of end-stage renal disease. Both of these conditions are manifestations of diabetic microvascular disease and, hence, would greatly benefit from a clinical tool that is able to predict patients at risk for disease progression and can monitor oxygen supply and demand in real time. We will test the hypothesis that imaging of the retinal metabolic rate of oxygen, using an innovative OCT approach, can provide a much-needed, non- invasive biomarker of diabetic microvascular disease. In this proposal, we will establish a normative database of retinal metabolic rate in healthy subjects, before proceeding to examining diabetic patients with various complications of diabetic retinopathy before and after pharmaco-therapy. We hypothesize that functional imaging will be able to explain the response to pharmaco-therapy, as well as correlate with diabetic microvascular disease stages. In addition, we will explore the potential renal effects of antiVEGF on this population of patients using rigorous monitoring of renal function. The experiments proposed herein will capitalize on the interdisciplinary expertise of the PI's at Northwestern University. Dr. Fawzi is an NIH-funded clinician-scientist retinal specialist with special expertise in retinal imaging and retinal vasculr diseases. Dr. Zhang is an NIH-funded biomedical engineer, member of the ANSI laser safety committee whose expertise is in functional optical imaging and novel retinal imaging tools. Dr. Zhang has an established laboratory at Northwestern, with strong collaborative ties to Dr. Fawzi, as they share an NIH-funded research program. The current proposal will allow these researchers to validate their proof-of-principle animal data. The research collaboration includes co-I Dr. Jampol, a world-class ophthalmologist clinician-scientist. Nephrologist, Co-I (Dr. Quaggin) is a world-class clinician-scientist and expert on the glomerular function of VEGF and its signaling partners. In addition to fulfilling an important and clinically relevant need, succes of this proposal will provide quantitative tools to study retinal blood flow, oxygen delivery and extraction, in addition to vessel area, allowing researchers to study functional relationships between retinal vessel geometry and systemic micro- and macro-vascular diseases. We believe that our proposal will provide a paradigm shift in patient management, as well as greatly improve our understanding of the pathophysiology of diabetic retinopathy.